Long non-coding RNA HOTTIP promotes hypoxia-induced epithelial-mesenchymal transition of malignant glioma by regulating the miR-101/ZEB1 axis

Zhang, Shanyi; Wang, Weiwei; Liu, Guoxin; Xie, Shuhua; Li, Qunxing; Li, Yingru; Lin, Zhaoyu

doi:10.1016/j.biopha.2017.08.133

Cited by 72 publications

(49 citation statements)

References 43 publications

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“…26,27 HOTTIP prevented glioma progression by sponged endogenous miR-101 and inhibited its activity, further F I G U R E 9 The expression levels of three long noncoding RNAs in gastric cancer tissues resulted in increased ZEB1 expression and promoted the process of EMT. 28 In hepatocellular carcinoma, HOTTIP can be negatively regulated by miR-125b, while miR-192/-204-HOTTIP axis may interrupt HCC glutaminolysis through GLS1 inhibition. 29,30 The expression of lncRNA UCA1 has been reported to be upregulated in many cancers, including breast cancer, 21,22 colorectal cancer, 31 hepatocellular carcinoma 32 and GC.…”

Section: Discussionmentioning

confidence: 99%

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

Zhang

Jiang

et al. 2019

J of Cellular Biochemistry

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Gastric cancer (GC) is a prevalent malignant cancer of digestive system, identification of novel diagnostic and prognostic biomarkers for GC is urgently demanded. The aim of this study was to determine potential long noncoding RNAs (lncRNAs) associated with the pathogenesis and prognosis of GC. Raw noncoding RNA microarray data (GSE53137, GSE70880, and GSE99417) was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes between GC and adjacent normal gastric tissue samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Differentially expressed genes were further confirmed by The Cancer Genome Atlas (TCGA) database. Competing endogenous RNA (ceRNA) network, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway, survival analysis were extensively applied to identify hub lncRNAs and discover potential biomarkers related to diagnosis and prognosis of GC. In total of 246 integrated differential genes including 15 lncRNAs and 241 messenger RNAs (mRNAs) were obtained after intersections of differential genes between GEO and TCGA database. ceRNA network comprised of three lncRNAs (UCA1, HOTTIP, and HMGA1P4), 26 microRNAs (miRNAs) and 72 mRNAs. Functional analysis revealed that three lncRNAs were mainly dominated in cell cycle and cellular senescence. Survival analysis showed that HMGA1P4 was statistically related to the overall survival rate. For the first time, we identified that HMGA1P4, a target of miR‐301b/miR‐508, is involved in cell cycle and senescence process by regulating CCNA2 in GC. Finally, the expression levels of three lncRNAs were validated to be upregulated in GC tissues. Thus, three lncRNAs including UCA1, HOTTIP, and HMGA1P4 may contribute to GC development and their potential functions might be associated with the prognosis of GC.

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Section: Discussionmentioning

confidence: 99%

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

Zhang

Jiang

et al. 2019

J of Cellular Biochemistry

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“…9 It has been reported that EMT in GBM is the key factor for its invasion and malignant behaviours 7 ; however, the mechanism behind this activity remains largely unknown. 9 It has been reported that EMT in GBM is the key factor for its invasion and malignant behaviours 7 ; however, the mechanism behind this activity remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

Liu

et al. 2019

J Cellular Molecular Medi

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Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial‐mesenchymal transition. Long intergenic non‐coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up‐regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreover, ectopic LINC00511 enhanced GBM cells proliferation, EMT, migration and invasion, whereas LINC00511 knockdown had the opposite effects. Mechanistically, we confirmed that ZEB1 acted as a transcription factor for LINC00511 in GBM cells. Subsequently, we found that LINC00511 served as a competing endogenous RNA that sponged miR‐524‐5p to indirectly regulate YB1, whereas, up‐regulated YB1 promoted ZEB1 expression, which inversely facilitated LINC00511 expression. Finally, orthotopic xenograft models were performed to further demonstrate the LINC00511 on GBM tumorigenesis. This study demonstrates that a LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop provides potential therapeutic targets for GBM progression.

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“…More than CASC9, a large number of lncRNAs have been reported. For instance, lncRNA HOTTIP is up‐regulated in glioma cells treated by hypoxia, and knockdown of HIF‐1α and HOTTIP blocked hypoxia‐induced EMT, and suppressed invasion and migration of glioma cells by regulating the miR‐101/ZEB1 axis . HOXA11‐AS is significantly up‐regulated in glioma tissues and cell lines and its knockdown inhibits glioma cell proliferation, migration and invasion in vitro, and tumour growth in vivo, thereby via ceRNA for miR‐214‐3p and its direct target EZH2 …”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA CASC9/miR‐519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

Liu

Yang

et al. 2018

J Cellular Molecular Medi

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Emerging evidence have illustrated the vital roles of long noncoding RNAs (lncRNAs) in glioma. Nevertheless, the majority of their roles and mechanisms in gliomagenesis are still largely unclear. In this study, we investigate the roles of lncRNA CASC9 on glioma tumourigenesis and authenticate its potential mechanisms. Results manifested that CASC9 was highly expressed in glioma specimens and cells, moreover, the ectopic overexpression was correlated with glioma patients’ clinic. Functional studies found that siRNA‐mediated CASC9 silencing inhibited the proliferative ability, invasion in vitro, and impaired the tumour growth in vivo. Mechanical studies revealed that miR‐519d both targeted the 3′‐UTR of CASC9 and STAT3 mRNA, which was identified by luciferase reporter assay and RNA immunoprecipitation (RIP). Moreover, chromatin immunoprecipitation (ChIP) and luciferase reporter assay revealed that STAT3, an oncogenic transcription factor, could bind with the promoter of CASC9 and activate its transcriptional level. In conclusion, our results concluded that CASC9 promotes STAT3 expression via sponging miR‐519d, in return, STAT3 activate CASC9 transcription, forming a positive feedback loop of CASC9/miR‐519d/STAT3. The novel finding provides a potential therapeutic target for glioma.

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Long non-coding RNA HOTTIP promotes hypoxia-induced epithelial-mesenchymal transition of malignant glioma by regulating the miR-101/ZEB1 axis

Cited by 72 publications

References 43 publications

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

Long noncoding RNA CASC9/miR‐519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

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